Aortic stenosis is a common heart valvular disease whose pathological processes include an inflammatory reaction and lipid accumulation. However, its detailed pathogenesis is yet to be completely elucidated. Therefore, it is of great significance to further explore the molecular mechanisms of aortic stenosis. Four datasets were downloaded from the Gene Expression Omnibus (GEO) database. Firstly, the differently expressed genes (DEGs) were screened between control and aortic stenosis samples. Secondly, weighted gene co-expression network analysis (WGCNA) was performed to find the highly relevant gene modules. Enrichment analysis and protein-protein interaction (PPI) networking were also performed, then Cytoscape was used to identify hub genes. Finally, the six participants (3 control participants and 3 patients with aortic stenosis) were recruited at the Tianjin Chest Hospital. In order to verify the expression level of USP14, several molecular experiments were performed, including hematoxylin-eosin (HE) staining, immunohistochemistry, immunofluorescence technology, real time-quantitative polymerase chain reaction (RT-qPCR), and western blotting. A total of 9636 DEGs were found between the control and aortic stenosis samples. The DEGs were mainly enriched in the autophagy-animal, cellular lipid catabolic process, apoptosis, and glycoside metabolic process categories. Eleven hub genes were identified via four different algorithms. Following verification of the patient samples, Ubiquitin-specific protease 14 (USP14) was found to be displayed at higher levels in the aortic stenosis samples. USP14 might be involved in the occurrence and development of aortic stenosis, so it would be a molecular target for early diagnosis and specific treatment of aortic stenosis. There is a significant association between the high expression of USP14 and aortic stenosis, indicating that this gene may be a genetic risk factor for aortic stenosis.

中文翻译：

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泛素特异性蛋白酶作为主动脉瓣狭窄的潜在基因生物标志物。

主动脉瓣狭窄是一种常见的心脏瓣膜疾病，其病理过程包括炎症反应和脂质蓄积。但是，其详细的发病机理尚未完全阐明。因此，进一步探讨主动脉瓣狭窄的分子机制具有重要意义。从Gene Expression Omnibus（GEO）数据库下载了四个数据集。首先，在对照和主动脉瓣狭窄样本之间筛选差异表达的基因（DEG）。其次，进行加权基因共表达网络分析（WGCNA）以找到高度相关的基因模块。还进行了富集分析和蛋白质-蛋白质相互作用（PPI）网络，然后使用Cytoscape鉴定轮毂基因。最后，天津胸科医院招募了6名参与者（3名对照参与者和3名主动脉瓣狭窄患者）。为了验证USP14的表达水平，进行了一些分子实验，包括苏木精-伊红（HE）染色，免疫组织化学，免疫荧光技术，实时定量聚合酶链反应（RT-qPCR）和蛋白质印迹。在对照和主动脉狭窄样本之间共发现9636个DEG。DEGs主要集中在自噬动物，细胞脂质分解代谢过程，细胞凋亡和糖苷代谢过程类别中。通过四种不同的算法鉴定了11个中枢基因。在对患者样品进行验证之后，发现在主动脉狭窄样品中泛素特异性蛋白酶14（USP14）的含量更高。USP14可能参与主动脉瓣狭窄的发生和发展，因此它将成为早期诊断和特异性治疗主动脉瓣狭窄的分子靶标。USP14的高表达与主动脉瓣狭窄之间存在显着关联，表明该基因可能是主动脉瓣狭窄的遗传危险因素。